A Long History

Although altered EBV-specific antibody titers have been repeatedly demonstrated in CFS, no clear evidence for chronic EBV replication has been obtained so far. Authors

Perhaps the most common viral trigger for chronic fatigue syndrome (infectious mononucleosis, aka glandular fever) or Epstein Barr Virus (EBV) is a herpesvirus almost all adults have been exposed to and carry, usually in latent form in their cells.

Conflicting results have made it difficult to determine the role EBV plays in ME/CFS. Will this German study signal a change?

EBV infection was proposed as the cause of chronic fatigue syndrome not long after the disorder became prominent in the 1980s, but inconsistent study results in the 1980s and 1990s followed by Straus’s 2000 paper (which suggested the search for herpesvirus infections in ME/CFS was over) put a damper on EBV research efforts.

From 2000 to the present only Dr. Lerner with his stream of positive studies (but sometimes challenging study designs) and Dr. Glaser published fairly consistently on EBV in ME/CFS. Recently Dr. Lipkin stated (unpublished) he found no evidence of active EBV infection using high throughput sequencing in the plasma of hundreds of ME/CFS patients.

Despite study inconsistencies, EBV has remained a pathogen of interest in ME/CFS. Both Lerner and Glaser have produced evidence suggesting that a defective form of the EBV virus may be causing the symptoms in some people with ME/CFS. Recent studies suggesting that EBV triggers autoimmune disorders are intriguing given the successful ME/CFS Rituximab treatment trials.

EBV’s ability to reactivate during stress and in hypoxic conditions may have implications for its possible role in ME/CFS as well. A recent laboratory study suggesting that high rates of oxidative stress can reactivate EBV and that antioxidants (including NAC, catalase, and L-glutathione) might be helpful in reducing EBV reactivation is intriguing given the high rates of oxidative stress found in ME/CFS.

Now, in a surprising turn, German researchers have not only put the spotlight back on EBV, but have dug deeper into EBV, ME/CFS, and the associated immune response than any group has before.

The Study

The adaptive part of the immune system, the one that takes time to kick in, comes in the form of B-cell produced antibodies that lock onto proteins the virus produces and cytotoxic T-cells that attempt to the kill the virus. (B-cell’s attack the virus in the blood and cytotoxic T-cell attack virally infected cells.)

Ohio State researchers believe a defective form of EBV that is spewing out proteins may be causing ME/CFS

Noting some unusual findings in their lab, these researchers looked at these antibodies and T-cells to see if people with chronic fatigue syndrome were mounting an effective immune response against EBV. They also looked for direct evidence of an active EBV infection.

EBV replication occurs when the virus produces proteins in a sequence that allows it to build another virus. One theory, developed by Dr. Lerner and a group at The Ohio State University (that includes Drs. Ariza, Glaser, and Williams), proposes that EBV undergoes ‘abortive replication’ in some people with ME/CFS. In abortive replication, a defective form of EBV produces early proteins, but is unable to produce later ones. The Ohio State group believes continual production of these proteins is causing a chronic inflammatory state in some people with ME/CFS.

Results

First, the German researchers found evidence of primary EBV infection or reactivation (increased IgM antibodies to a late EBV protein in @15% of patients vs 3% of controls) in significantly more ME/CFS patients than controls. The fact that this could be a ‘primary infection’; i.e. it represents the first time these patients are exposed to the virus is intriguing. A primary infection of EBV early in life usually leads to nothing more than a cold; a primary infection later in life can have serious consequences including infectious mononucleosis.

Having found evidence that an active EBV infection was more common in people with ME/CFS than controls, they looked to see if a reduced immune response was responsible for that.

The first hint of a reduced immune response to EBV in ME/CFS came in the form of a lack of antibodies to EBV-produced proteins VCA and EBNA1.

But first, a short antibody primer:

Antibodies attack pathogens in the blood; cytotoxic T-cells attack them in the cell

Antibody Types

IgG antibodies are ‘memory antibodies’ that travel through our system looking for evidence that a pathogen is present. Once your B-cells have mounted an attack against a pathogen, they are always present in our system. Therefore, IgG antibodies are not evidence of an ongoing infection.

IgM antibodies are attack proteins associated with a pathogen. High IgM titers to a viral protein generally reflect a primary infection.

With two types of antibodies being manufactured against a range of viral proteins the situation becomes complicated, but a healthy immune system should produce an array of both IgG and IgM antibodies that can detect (IgG) and inhibit (IgM) pathogens (found outside cells) at different stages of their lifecycles.

As they dug deeper, the German researchers found holes in the immune response to EBV in ME/CFS patients.

Immune Holes to Epstein-Barr Virus Found

Immune Hole #1 – reduced antibody response

Evidence of a impaired B-cell response to EBV first came in the form of missing IgG antibodies to VCA and EBNA in 13% of ME/CFS patients compared to 4% of controls. This indicated that 13% of their ME/CFS study population did not have some of the memory B-cells needed to detect an EBV infection.

Increased IgM antibody responses in ME/CFS (17.5% in ME/CFS vs 4% in controls), on the other hand, suggested active and perhaps primary EBV infections were more commonly found in ME/CFS patients.

All told, 30% of the ME/CFS patients either had reduced IgG (EBNA-IgG) or increased IgM (VCA) responses to EBV.

That finding prompted a deeper look, and a much larger study that found no IgG response to a protein expressed during latency by EBV (called EBNA-1 protein) in 10% of IgG positive ME/CS patients. This indicated that the immune systems of approximately 10% of the ME/CFS group were unable to detect a very early stage of EBV latency.

The EBNA-1 protein featured in many of the tests helps EBV maintain its latency in B-cells

Latency – For EBV to maintain itself in the body over time, it needs to be able to maintain itself in B-cells in a process called latency. EBNA-1 is a protein that helps maintain EBV’s viral genome in the earliest stages of latency.

The authors noted that people with severe infectious mononucleosis and chronic active Epstein-Barr virus disease have similar findings (although it’s not clear why, given that EBNA-1 is not involved, so far as we know, in replication).

That brings up the question of how many people with ME/CFS would have fit into the category of severe mononucleosis at the time they got ill. The Dubbo studies found that more severe infections greatly increase the risk of coming down with ME/CFS.

Intrigued by the findings, the German researchers dug deeper into the immune response to EBV. They took blood (PBMCs) from ME/CFS patients and then stimulated it with CpG, SAC, and PWM for seven days, and found reduced frequencies of B-cells producing antibodies against VCA and EBNA-1, and for the first time they found evidence of immune deficiencies in most people with ME/CFS.

No less than 59% of ME/CFS samples had a diminished response to a later stage EBV protein (VCA) produced during the late stage of lytic replication, and a whopping 76% of ME/CFS samples had a diminished response to the EBNA-1 protein. With the VCA finding we have evidence suggesting many people with ME/CFS may have trouble controlling EBV replication.

Calling the findings ‘remarkable’, the authors suggested that either the memory B-cells associated with these EBV antigens had been lost or had failed to develop into antibody-secreting cells.

Immune Hole #3 – Reduced T-cell response to EBNA-1

A similar deficiency in the T-cell response to EBNA-1 indicated that both arms of the adaptive immune response to Epstein-Barr Virus, the B-cells and the T-cells, had difficult recognizing and responding to this protein.

Citing other disorders such as HIV, they suggested that persistent EBV reactivation in ME/CFS had driven the T-cell response in ME/CFS into ‘exhaustion’. (A similar suggestion has been made with regard to natural killer cells that attack pathogens early in an infection, which use killing methods similar to those employed by T-cells.)

Further analysis suggested that T-cell suppressor cells which decrease B-cell responses were not responsible for the B-cell suppression found. Normal B-cell responses to herpes simplex and cytomegalovirus suggested that the deficient B-cell responses were associated with EBV and not other herpesviruses.

Lower cytotoxic T-cell responses to EBNA-1 could be associated with an increased risk of autoimmune disorders

Next they explored T-cell induced cytokine production. The T-cells should produce an array of cytokines against EBV. About 20% fewer ME/CFS patients (70% of controls vs 50% of ME/CFS patients) were able to mount an IFN-y response against EBV.

Looking specifically at the latency associated EBNA-I protein, they found the startling result that no ME/CFS patients mounted an IFN-y response against it.

They also found that ME/CFS patients produced significantly lower amounts of the pro-inflammatory cytokine TNF-a in response to EBV. Finally, a lower percentage of patients produced IL-2 as well. The reduced cytokine production suggested cytotoxic T-cells, one of the big guns of the adaptive immune response, were not being strongly activated in response to EBV.

Immune Hole #5 – Reduced frequencies of EBNA-1 specific T-cells

The researchers dug deeper still. Next they stimulated the blood (PBMCs) of ME/CFS patients and healthy controls (n=40) with the EBNA-1 protein, expanded the cells in the presence of IL-2 and Il-7, and then checked the T-cell response to them. Specific types of T-cells should be produced to attack EBV, but reduced frequencies of EBV-specific T-cells occurred in about 50% of the ME/CFS samples. That again suggested the cytotoxic T-cell response to the EBNA-1 protein was substantially reduced in ME/CFS.

Direct Evidence of Active EBV Infection

“Remarkably, in line with this finding we could provide evidence of enhanced viral load of EBV by detection of EBV DNA in a significantly higher proportion of patients compared to healthy controls.” The authors

Using a real-time PCR test in the whole blood that looked for ‘low-copy’ numbers (<1,000-2930 copies/ml) they found evidence of increased EBV viral load in 7.2% of 290 ME/CFS patients. When they dug deeper and did the same test in PBMCs in a subset of patients, they found that a whopping 55% of patients (vs 13% of controls) tested positive for EBV.

The viral loads were far below those found in other EBV associated illnesses such as infectious mononucleosis or post-transplant EBV infections, and there was no evidence of lytic replication (i.e., full replication of the virus), but something the authors called ‘latency-associated replication’ was common in people with ME/CFS, yet not in healthy controls.

The Lipkin Study

Using PCR the German researchers found much higher rates of EBV infection in PBMCs vs whole blood and no evidence of EBV infection in plasma.

Was looking for EBV in plasma somehow a mistake?

Neither the Lipkin CFI ME/CFS pathogen study nor the CFIDS Association of America BSR study found evidence of EBV infection in ME/CFS. According to Russell Fleming’s transcript of the Lipkin talk, the CFI study looked in the plasma of both the Montoya and the ME/CFS experts’ samples.

EBV DNA has certainly been found successfully in plasma before and plasma has been used to track EBV activation. Serum/plasma EBV PCR kits are available for purchase. Researchers search and find EBV in plasma frequently.

Dr. Chia, however, reportedly stated he believes the use of plasma rather than blood was a serious mistake, and the Germans were able to find evidence of EBV activation in blood but not in plasma.

EBV (and CMV and HHV-6) are ‘cell-associated viruses. The only times their DNA escapes the cells is when the cell dies (and the DNA goes into the plasma) or when the virus is replicating. Otherwise the virus sits in a latent or semi-latent state in the cells

Medical dogma states if you can’t find EBV in the plasma, the infection is not active. EBV DNA can be found in the plasma when EBV replication rates are high, as sometimes occurs in transplant patients, but it’s not likely to be found in the smoldering infection believed present in ME/CFS. Many researchers do not accept the idea of a smoldering infection that pumps out proteins which trigger an inflammatory response.

The German researchers are deepening their study of EBV and ME/CFS and currently evaluating antibody responses against a broader variety of EBV peptides derived from 8 different proteins. They are also quantifying the levels of memory B-cells targeting EBNA-1 and VCA.

Conclusion

“We think the altered pattern of the specific immune response to EBV may be suitable as a diagnostic marker for CFS.” Authors

The harder they looked, the more they found …

It was if these researchers kept pulling a string that got longer and longer. First their interest was piqued by some paradoxical antibody findings, then they found widespread deficiencies in some antibody responses and T-cell responses, and finally they saw evidence of an active EBV infection in the blood of 55% people with ME/CFS (vs 7% of controls).

Much is still unclear. The EBNA-1 protein that the immune systems of ME/CFS patients had trouble responding to is associated with ‘early latency’, not EBV replication. The authors’ reference to ‘latency associated replication’ is unclear given that latency is not usually associated with replication. When asked what importance their findings have for EBV reactivation or EBV survival or more severe casesof infectious mononucleosis in ME/CFS, the authors stated they can’t answer those questions yet.

Some researchers believe, however, that reduced cytotoxic T-cell responses to EBV increase the risk for autoimmune disorders. (We’ll be covering that possibility in the next blog.) These findings also suggest that the proposal by Lerner and the OSU group of Drs. Ariza, Glazer, and Williams that an abortive lytic process (smoldering EBV infection) is present in many people with ME/CFS may be correct.

While it will take more work to determine what these findings mean for ME/CFS, the broad range of dysfunction found and the high rate of active EBV infection (in plasma) would appear to put this pathogen back into play in a meaningful way in ME/CFS.

Cort Johnson

LeJean Sommerville

Hi Curt, Thank you for your informative and in-depth research on this subject. On May 7th 2015, a confirmation of reactivation of EBV was diagnosed from blood sample. Titer levels for EBV were >600… My Dr. stated the norm was <18. My first EBV (known as Mono then) was confirmed @30 years ago. It went "away" and to my knowledge has surfaced presently with a vengeance. I am off work because of all of the usual symptoms presently… My doctor. stated that I had Reactivated EBV w/ CFS. Treatment is Rest, Rest & Rest… I have primary symptoms of: chronic swollen lymph nodes, sore throat, fatigue, some joint discomfort, very high sensitivity to light, with headaches and mild fever… etc. I am still quite ill.

So, my question, is there anything else you can recommend for me to help treat this? My physician only stated that this was going to be a long process for me, and to rest, eliminate stress, and a leave from work for 4-6 weeks with a re-examination at that time. I am currently at around week 6 – and still quite ill. This is a surprise tome.

Any suggestions you could offer to me would be greatly appreciated.
Thank you,
LeJean

julia van schalkwyk

HaLlo Cort, it has been a long time since I left a reply. I am a accute EBV patient, and recemtly been diagnosed with liver hemangiomas, and mr scans showed no change there. I would like to know what role high uric acid has to play in accute ebv. Would it help if I try and follow a good anti-gout diet in keeping my t and b cells in better readings, and helping to fight the ebv better. I mentioned at that time that I got rid of the cfs for the first time in years, as soon as I start using the beriglobin, but after 6 months I stopped that, due to the fact that my specialist said it made my immunity system “lazy”. Can you reflect. On the uric acid please?

A study is a great example that we, the me/cfs community, can rejoice in the progress that is made in areas of research unrelated to ME/CFS.

I bet a lot of money and time went into developing the tests that these researchers were able to adapt with relatively little effort to their ME/CFS research.

Likewise, the XMRV findings used knowhow that was developed with the millions of dollars that go into cancer research.

Unfortunately, right now the research budget is even too small to translate breakthroughs from other areas into breakthroughs in ME/CFS.

Still,, it gives me great hope that when we are able to come up with a decent research budget ourselves, we won’t have to reinvent the wheel, but can instead build on the progress made in other areas of medical research.

Cort Johnson

If that’s Andrew Lloyd I’d love to hear what he has to say. He does have very high standards. I remember him telling a conference full of researchers that they were pretty much full of it on one topic. Sometimes he’s right! 🙂

Claudia Heath

March 13, 2014 at 11:19 pm -

The very same. The response you heard is typical. I am scientifically useless but I can at least hear his opinion. Next appointment is beginning of May so I’ll feed back to you then. He is just pubishing results of his own longitudinal research from the NSW Uni Lifestyle Clinic Fatigue Program so that will be of interest to discuss, too.

Cort Johnson

K. Brown

I can’t describe how excited this makes me. I read Dr. Lerner’s research as far back as 2008 and thought his theory was quite possible. He also was one of the first I’d known of to give Valcyte or Valtrex and at that time he had a better rate of cure or vast improvement of his study patients than anyone. I believe his work was the basis of Dr. Montoya and Koeglenik’s work which also helped many in their small studies. I hope they have or get the money they need to continue this most exciting research. I want to send them flowers or something. Wow, this seems to be giant news in my opinion. I wondered if getting blood transfusions of someone who had the proper immune responses to EBV could alleviate the symptoms of those of us with ME/CFS. Can’t wait til they find out more.

Cort Johnson

I talked to researchers associated with Dr. Lerner at Ohio State University. They did not agree with all the interpretations (latency associated replication) but they did feel the finding fit with Lerner’s hypothesis.

I think it’s pretty darn big news; nobody has looked at EBV like this before in ME/CFS. The German researchers are going to dig deeper. It’s going to be very interesting and hopefully this research will spark more research in the US. I’m going to try to snag Montoya and others and ask them about this paper and Symposium and conference.

K. Brown

I don’t see how these findings couldn’t be big news. Hopefully this doesn’t slam into the ground the way XMRV did. If our genetics are what cause the inability of the immune system to fully squash an EBV infection I wonder what the treatment or cure might be for that. I know, it’s too soon to be getting that hopeful, but I just can’t help it. When was there anything this explicit in the bloodwork of ME/CFS?

Kathy

In my early days after diagnosis, 33 years ago, my blood tests showed suspicious ebv activity and considering I’d had a particularly severe case of mono at age 13 I’ve always presumed ebv and me/cfs are related. Though at the time ebv was a topic of conversation in the community it wasn’t given any legitimacy by the medical/research fields. Probably another case of valuable time being lost in the quest to understand/cure this illness being strangled in its infancy since after all it only affected over achieving ‘yuppies’ -/ sarcasm off.

Cort Johnson

Paul

I had a bad sore throat of epic proportions 18 years ago. From doing 1 to 2 hours exercise a day I found it exhausting to walk up the stairs to have a wee. Blood tests showed millions of white blood cells and the Doctor smiled and said that I would have some good days and that over time; the bad days would be less and the good days grow into longer spells. So 18 years later I have never been able to reach a good level of aerobic exercise, but I do go to work. -I am knackered when I get home and ache, if I rest a lot I am OK and if I feel well I go the gym twice in a week. I sometimes feel perfectly well, but that is rarely more than for two to three hours -the rest of the time i feel fatigued etc.etc.etc.if I dont rest my lymph gland swell and cause discomfort and my muscles ache. I am so fed up with being a hypochondriac and apologizing for not doing things socially or around the house.. Iam truly upset by it. HOWEVER, when the lymphs are swelling and its worse I eat two desert spoons of coconut oil a day- trust me that works. more regularly I take a form of enzyme q10 for over 50s that helps too. Trust me coconut oil will help…….anyway that’s my experience hope it helps you or someone.

Marg

Thanks Cort, this article was amazing. It sounds just like my first visit with Dr. Klimas and her explaining all and the how the whole thing was suppose to work but it was not.. My EVB titers were very high and the T and B cells not very good. My immune system was broken!

Kathy you and I got sick at about the same time and the first doctors I went to would not even test for EVB, too controversial so they said and everyone had it over 30. Years wasted…I did with a lot of work on my part and a naturopath have and 8 year remission but it came back 5 years ago. I am doing well with Imunovir but have started having trouble with Acyclovir. I was told a side effect is uric acid and I will be tested when the papers arrive. I think that is it…burning pain and when I stop it goes f down 77%. I started and stopped 3 times and the same response… Here is to the “Yuppi “Flu!

Chris

I’m thinking of Erik who did not have the EBV titer response that others showed, yet he was pretty much as sick as everyone else before he got out of Dodge and began avoiding what some believe are mold toxins. Granted, Glaser et. al. and the Germans are now looking at new parameters; I wonder if EBV is really the primary trigger or just another degree of disruption with its own consequences that he hadn’t reached yet, maybe. I wish there was a way to go back in time an look anew. Treating the herpes infection works for some; so many chicken-and-egg questions.

Eilidh Hewitt

EBV makes such sense; could it be that the cause of ME has been hidden in plain sight all along, something so obvious it has just been ignored? Often the solution to a problem is beautiful in its simplicity even though the initial problem seems so complex.

So many cases of ME are triggered by Glandular Fever and the time lag of a latent infection could account for the others. It could be behaving like Hepatitis C or as Polio did in the past. Glandular Fever has a reputation for incomplete recovery and for recurring. In sport they know about its potentially destructive nature and athletes can be advised to take a year off to rest and recover. Glandular Fever can be a very nasty infection indeed and the possibility of long term complications seems to be hugely underestimated.

I think the most significant recurring symptoms in ME are; sore throat and painful swollen glands in the neck and arm pits with bodily aches and mild fever. I have often thought that these symptoms must be a sign of persistent infection.

Its 25 years since myself and three of my children, fell ill with Severe ME after Glandular Fever. In all these years I have never heard of anything that has had more potential as a possible cause for ME as EBV and Glandular Fever and I imagine the Vagus Nerve Hypothesis would fit in with it.

17 years after developing ME my three children went on to develop other serious disease. One has Gastroparesis (paralysis of the stomach) a connection here with the Vagus Nerve as it controls the stomach. Another has developed MS and Ulcerative Colitis and the third Coeliac disease and Keratoconus (eye disease of the corneas). My niece also became ill with ME after Glandular Fever and she went on years later to develop intractable Inter-cranial Hypertension that has to be controlled by shunts.

NHS Choices; “Someone with Glandular Fever is contagious for at least two months after initially being infected with EBV. However, some people can have EBV in their saliva for up to 18 months after having the infection. A few may continue to have the virus in their saliva on and off for years”.

Wikipedia; “fatigue and a general feeling of being unwell may sometimes last for months.[6] Fatigue lasts more than one month in an estimated 9–22% of cases.[3] In cases where fatigue lingers, it generally passes spontaneously within 2 years.[3] Mild fever, swollen neck glands and body aches may also persist beyond 4 weeks.[6][9][10] “

Eilidh Hewitt

Thank you Cort you have done a very fine job on this EBV Glandular fever article and I will certinly be looking out for the next one.

To answer your question; This is something that puzzles me because my children were young when infected with Glandular Fever but had a disasterous outcome. Two had Glandular fever at 10 and 11 years of age and the the other, who now has MS and Ulcerative Colitis, was 6, tested positive at the time. The MS paper link I included fits with his experience. We have heard of other severe childhood sufferers who have had the same experience of developing other conditions just as they were recovering.

Ann

After reading your concise, informative and very moving account of your family’s illnesses, I can only hope that it has given you a small amount of relief, to let others know the exact realitiy of suffering from ME.

With so many conditions relating to ME, your story shows the stark, unstripped version of life with this illness and I would imagine many people reading this will have their eyes opened wide. The very nature of the illnesses, within your family alone, cannot help but move the most sceptical mind.

You will always be my source of inspiration and my guidance through this terrible disease.

You are the true angels of this world and I pray that EBV is found to be the answer to all our prayers, with a cure to follow.

Cort, This lady has been our bible, here in this part of the UK and when she speaks, I know it’s important to listen. Thank you Eilidh and thank you Cort for allowing this forum.

I’m pleased to say Eilidhis a true friend and honoured to know her and her family.

Lots of love
Ann O’Connellxx

Eilidh Hewitt

March 15, 2014 at 2:03 pm -

Thank you Ann
For your support and very kind words. Especially poignant knowing your history, how ill you are yourself with ME and also how you have other family members affected as well.
It’s always an honour and a great help to share times of trial with good friends, people that understand each other and the awful hardships and feats of endurance forced on us, that inevitably come with ME.
Love and best wishes to you and your family
Eilidhxx

Simon McGrath

Jean

I was very ill in 1993 (Fall)
Diagnosed of FMS 1994 at a Boston Hospital, have tried my best to live with it, although it is not the living I once had.
I found this article very interesting, as my partner (retired psychiatrist) , came down with EBV, / Mono age 50, after which he never fully recovered, and was told he had FBS.
We both also have extensive OA, I am 56 and he is 62, is there any connection???
Please, and Thank-you.

Cort Johnson

What I am learning about EBV is that if you have a primary infection at any other time than childhood you could be in trouble. A primary infection (i.e. the first time you’re exposed) in adolescence may very well end up in a case of infectious mononucleosis – which greatly increases your risk of coming down with ME/CFS or multiple sclerosis. If your partner’s primary infection was at age 50, his immune system probably wasn’t able to deal with it. Our immune systems as infants are actually far stronger than they are as adults.

Infants usually have no problems with EBV; in fact, they don’t even notice it – their immune systems quickly take care of it.

The next blog is going to focus on EBV and autoimmunity – be sure to check it out.

Jean

Mike

“When they dug deeper and did the same test in PBMCs in a subset of patients, they found that a whopping 55% of patients (vs 13% of controls) tested positive for EBV.”

Why did they run PCR testing on PBMCs only in a SUBSET of patients, as opposed to the entire study sample? How did they select which patient samples would be included in the subset? Were they selected based on other characteristics that the researchers thought made it more likely that an EBV infection would be found? Or was it done randomly for practical/logistic reasons (e.g., it was too expensive to do this for the entire study sample)?

In other words, does the research imply that roughly 55% of ALL CFS patients could have EBV infection in their PBMCs? Or does it merely imply a 55% infection rate in a particluar SUBSET of CFS patients with characteristics distinguishing them from other CFS patients?

Mike

Ann

In response to the ages of Eilidh’s children developing serious diseases and them testing positive for Glandular fever at as young, in one case ,as 6 years of age, could this be part of the latency/contributing factorsargument, rather than late infection with EBV, causing serious disease? That is, if late teens develop EBV/glandular Fever, is it more likely that they are subjects of latency and reactivation from a childhood infection with EBV?

If children have EBV infection, but don’t go on to develop diseases, perhaps it could lie dormant until the reactivation is caused by other factors, in some cases, rather than the primary disease infecting at that later age. Teenagers are routinely checked for Glandualr Fever due to its prevalence at that age, where as I’m not sure children would be.

EBV also causes many cancers (ME Research UK). In particular Lymphomas, which can affect ME sufferers. Could connections be made here I wonder?

Ann OConnell

Jacque

Sure rings true to me… My EBV and HHV6…HSV! and 1 titres are through the roof…and NK Cells in the toilet…. I found the hypoxic comment interesting..as I cannot fly if I EVER do get to travel or I get terribly ill.. I also get terribly ill in high altitudes!! Very interesting…. Thank you for all you do to keep us informed Cort…. Why does this have to be soooo complicated? I read every article with tears of pain and frustration streaming down my cheeks. My son who is 24 has MANY of the mysterious symptoms and I am just sickened even more to know this may be his life too… I hope not…I hope they get a handle on this soon…before half of our nation are “hypochondriacs who can’t go to work”!:(

Linda

My practitioner is currently helping remove EPV from my body with Chuan Xin Lian ( which i believe is Andographis) Huang Lian joe Du Wan and Lauricidin. This has been a big co-infection for me while fighting Lyme disease.

carlie

I currently have chronic ebv and was wondering if any of you have tried lauricidin? I also have problems with my family who tell me this is not a real disease or just doesnt exist. Its so hard to deal.

K. Brown

My bloodwork showed high titres of antibodies to EBV and this article explains why that is probably so. My immune system can keep it from being a full blown infection, but it can’t rid itself of some of the effects – if I understand correctly. I have so many symptoms its hard to ever know what causes any of them. If by lauricidin you mean monolaurin or lauric acid, I have recently begun to take it to see if it would have any effect on any of my symptoms. The one I KNOW it has helped in a profound way was the burning tongue I had. Almost anything I eat or drink caused my tongue to burn, it didn’t look red at all but inside if always felt like I had been drinking boiling hot coffee. I take 3-4 1,100mg capsules a day of monolaurin from coconut and now my tongue barely ever has a feeling of burning in it. If I quit taking them or miss one I can tell it’s still a problem, but as long as I’m taking at least 3 a day I am seldom aware of any burning sensation. Cytomegalovirus is one virus that lives in the tongue, I’m sure there are others, but my bloodwork also showed a high IGg level so I think maybe that is what the monolaurin works on – all supposition on my part, but it does help that. I hope if I stay on it I may find it helps other things as well over time. Supposedly kills “enveloped” viruses because it destroys the envelope of those viruses which kills them. The world of viruses is vast and complex. As for your family, I’m sure most of us can identify with that problem. The thing is, now there is enough medical proof of all the problems with so many systems in our bodies.
The brain, sinuses, throats, hearts, lungs, stomach, nervous system. If they still don’t believe after reading the latest evidence from researchers all over the world then they probably also think the sun revolves around the earth.

carlie

Cassandra

It took my doctor forever to figure out I even had EBV, because I didn’t have most of the usual symptoms – no sore throat, no elevated white blood cell count, no fever. I just felt awful. The only thing that tipped him off was that a CT scan showed some “lesions” on my spleen, and that led him to test specifically for EBV. The only explanation he could give was that some people’s immune systems just don’t respond to the virus the way they’re supposed to. Two years later I still haven’t fully recovered, and they’re calling it CFS. Interesting to see that there are other people following similar patterns.

BENARD FREDERIC

Lerner thought that antiviral did not target the latent/abortive infection, but some lytic infection that could infected cells and become abortive. So the idea is that the replicating virus are eliminated and the latent ones will clear with time. I don’t think that it works like that, I think antivirals can (badly) target the abortive infection that produces some viral proteins. But antiviral will not clear the latent/abortive infection, I don’t think.

I read also this story of a person with CFS that used immunotherapy and he was better, but can’t find the article. Immunotherapy is interesting for CFS.

Andrea

I was diagnosed with infectious mononucleosis at age 18. Since I was in college, I was still dealing with my pediatrician at the time. It was a fairly severe case and I was affected by the symptoms for a couple of years. Afterwards, the fatigue stuck around. Back then he diagnosed me with CFS, on the basis of the old belief that EBV could turn into EBS in some people and that EBS was synonymous with CFS at the time. Until recently, I’ve always believed this was true. Based on this research, it seems that although it might not work the way I understood it to, EBV does at least leave one susceptible to CFS.
In the following 18yrs I’ve been so sick with various illnesses. I’m now dealing with fibromyalgia, degenerative disc disease, osteoarthritis in my neck, ankylosing spondilytis, plus arthritis in other joints as well as bursitis and neuropathic pain issues (and debilitating migraines). My most recent bloodwork is fairly intriguing to me… the standard ANA titer is always positive, but I had extensive bloodwork for all autoimmune disorders and they are all negative.
This is my first time on this site and I’m thankful I found this research. I plan on attempting to catch up on all the reading here.

Lauren

Very interesting article. I am currently suffering from what the doctor calls “recurrent mononucleosis” brought on by stress. My EBV IgM, IgG, and EBNA were all high. I have been having very strange swelling of lymph nodes under my chin and down the front of my neck occurring cyclically, worse at the end of monthly cycles, plus colon issues and awful fatigue and headaches. I am currently also suffering through the second year of medical school. I wish I could take time to recover but the program is not conducive to that kind of delay. I hope the connections between EBV and ME/CFS are not true, but I have a feeling these studies are probably on to something correct. It is very frustrating being called by people close to you a “hypochondriac,” and for me I am glad they found the clinical symptoms of positive reactivated mono/EBV because it helps me prove to myself and others that I am not imagining this all, that something is actually going on medically.

Cort Johnson

Kathy

Hi Lauren, I’m sorry you’ve fallen into this world of post viral infection and all it can mean to one’s life. Many of us have histories of EBV infection. I had an extremely severe case of Mono – in hospital isolation for a week & very long convalescence – at age 13 then chronic appendicitis by age 17, which is thought to also have connections to EBV.

The period soon after initial infection is critical and getting as much rest and not pushing yourself beyond your limits will affect the outcome of how this all finally resolves itself in each of us.

Finally, I will never understand why we are thought to be hypochondriacs when most of us fight so hard to get our lives back to what they were before infection. It just shows the inadequacy of those who have no explanation but think they couldn’t be ignorant so we must somehow be at fault.

Hang in there Lauren, afflictions like this have the possibility of making each of us learn new ways of living that may after all be greater blessings than health.

Kathy

Marcia

I just discovered this site as I search for comfort after receiving the results of my recent labs. I was so disappointed to learn that my EBV titers are still through the roof after months of strict diet and antiviral supplements. I seem to have chronic disease and fear what I read about chronic active EBV. My results from the German lab (in July) showed very high numbers for both the lytic and latent phase activity. Will you help me understand the difference between the “fatal” chronic active EBV and chronic EBV. My doctor believes that I had mono when I was 20 (1970) and Lyme disease (since 2008) kicked the EBV into gear. Any insight would be appreciated. Marcia

Linda

Hi Marcia. I cannot answer regarding the difference between the fatal chronic EBV and this one, but there does seem to be a difference because the vast majority of CFS patients do not die of this, at least for a very long time.

With such high antibody titres, wouldn’t you be a candidate for antiherpetic drugs such as Famvir, Valtrex, Valcyte, etc?

Is your specialist in Europe?

Kathe

This study made me wonder what would happen if a CFS/ME patient received a blood transfusion from a “healthy control”. I wondered if their blood would make it clear the EBV virus, at least initially. I can’t wait for these German researchers to put out their next paper.

Marcia

Hi Linda, Thanks for your reply. I started on Famciclovir 10 days ago. I continue on herbals and turkey tail mushrooms. I take vitamin D, fish oil, vitamin C and magnesium as well. I do not allow myself alcohol or caffeine or added sugars. My doctor is in Albany New York and he sent my blood to a German lab. This doctor and my PCP both say I have the highest numbers they have seen. I wonder though, how many healthy people get tested for EBV as my symptoms have been very mild and mimic other conditions. Perhaps there are many people with very few symptoms who have high levels of EBV? I was tested because my friend, a microbiologist, was curious about my occasional severe fatigue days. Currently I’m able to carry on fairly well if I don’t get too stressed about my numbers. When I let the negative thoughts take over I feel pretty awful. On a positive note, all of my natural therapies have pushed my HDLS to 102 (almost unheard of) and I lost 10 pounds since my battle with the microbes began. I will post any progress or new treatments that come my way. My microbiologist friend is always coming up with new ideas. Her daughter has Lyme and EBV. Again, thanks for your reply. Marcia

JJ

I was wondering how you were doing and if you have any recommendations for doctors, especially infectious disease doctors in the Albany NY area. I seem to have chronic active EBV but my doctor is at a loss of what to do. Thanks!

julia van schalkwyk

I am suffering from EBV probably much longer that I know off. I had jaundice as a child, and apparently there are links between the herpes, hepatitis and some other diseases. In the last 6 months I have been diagnosed as having acute ebv. Still not sure what the difference is between chronic and acute. BUT I changed my dr and being under homeopatic treatment for the last 3 years with slow results (and always t-cell and b-cell changes) and low hopes on good readings on b and t cells, I decided to go to GP locally. And guess what, he said I should try the berryglobin injection from maerck labs in Switzerland. It is made up of healthy patient’s serum with good immunity. All you have to do is let your iGa tested. Mine was very low. I had immediate posiitve results with energy level back as when I was young again. I am 52 years now, and am having these injections for the last 3 months with the same good impact on my energy levels. Can use the treadmill again, and can begin with my life where I stopped living it due to cfs. The beauty of the berryglobin is that you don’t need a prescription for it, and that there are generic versions for it also, if not available! I came tohe conclusion that I don’t need to know my b- and t-cells anymore, which in itself have a neg impact on your life with an everlasting neg grip on life.

Cort Johnson

Ray Burch

I am new to this discussion. I had mononucleosis as a child. After I turned 40 I noticed the onset of unusual fatigue. After 14 years it has become constant and debilitating. I’ve been through several sleep doctors, endocrinologists, neurologists, and psychiatrists to no avail. I’m currently seeing a Dr. Castriotta in Houston. This is the most interesting read I’ve had in a long time.

julia van schalkwyk

My blood test results came back 4 days ago. I had my liver, kidneys, hepatitis C (I had jaundice as child), y iga, igm etc tested, and also ebv as well as glandular fever. The ebv is gone, no glandular fever, the only funny thing is my igm is very low. The iga and igm should always be actively working as first line of defence in viral infections. Can you give me some info here please. I am also considering to go gluten-free. I think part of my low immunity is poor nutrient absorption (mainly because I am a non-secretor) and I am trying to eliminate some possible culprits.

Kym-Louise

Hi Cort, thank you for this article. I was confirmed with adult ebv associated cfs – it has taken 4/5 years to get a doctor (ENT specialist actually) to test for certain autoimmunes etc, as I presented with many complex issues but always in the relentless cycle of evry 3-6 months there was a vicious coldsore – ear infection – throat infection – gut and digestive issues – sinusitis – fatigue and tiredness and depression – and because I was diagnosed with BPD (mental illness, years ago) the doctors overlooked many of my issues due to presenting with later, if you know what I mean. My ENT specialist has put me on 1000mg (1 morn & night) of vit C & E and 2000mg (same) Ginko Biloba & Echinacea and also 6 vit B shots. I’m so confused about about all the conflicting info out there and my mind just hasn’t been “with it”, if you know what I mean?… Anyway thanks again for sharing. It’s so good to finally have a more definitive answer to what’s been happening in my body, info like this helps clear the path a bit. Smiles and waves, Kymmilou 🙂

Kym-Louise

Todd F.

My primary care doctor told me 6 months ago that I had Chronic Active EBV. He began testing back in July and has tested several times since then. The antibody levels have continued to stay high. He tested me again last week but I have not heard any results yet. I have faith in my primary care doc, but realize that his knowledge in this area is limited. I have lived in severe joint pain and severe fatigue since 2006. I always think I just have to “suck it up” and work through it and that I might just be a little tired, but have never thought I had a medical reason for feeling so bad. Now, the more I learn about CAEBV the more depressed I get. I also have degenerative joint disease and will have fusion of three vertebra in my lower back in May. I am afraid my Chronic active EBV will inhibit my recovery from surgery and that I may never return to work again. I have felt so bad that I would just like to die. I would love to lie down to go to sleep and never wake up. i am not an unhappy person or a severely depressed person. i enjoy life and all it has to offer but I am just so tired I feel as if I cannot go on. I am trying to get an appointment at Vanderbilt University Medical Center, but I don’t even know what kind of doctor I should see. Any information would be greatly appreciated.

linda

i have had this for 22 yrs after EBV and have seen several of the top specialist.. if i were you, i would see Dr. Kenny DeMeirleir at either the Whittemore Peterson Institute in Reno or at Himmunitas in Brussels, Belgium. in the meantime, i would try valtrex or famvir for the high EBV load. i am not a medical professional..just have been through a lot with this illness.

Don Swindler

I had a liver transplant in 2007 and have enjoyed an active and illness free lifestyle until about 4 or 5 months ago. I found I was sleeping more during the day and did not have the energy to maintain my normal lifestyle. I thought that may be due to sleep apnea coming back after some weight gain (something i will have checked separately).

Last weekend, I woke up very sore with red blotches on my legs that were warm and tender to the touch. The next two nights, I was running a temperature of 100.4 (over 2 df over my norm of 97.8). Monday morning, I saw my primary care doctor and she ran a few blood tests and had me check into the hospital the next morning for testing.

That is when low levels of EBV were detected. I will be seeing an infectious disease specialist within the week, but from what I’ve read, there is no cure and one’s body usually handles the symptoms of the virus in time. I am concerned because a medically suppressed immune system doesn’t fight as well as a healthy one.

I appreciate the information here. I know we slow with age, but I hate the feeling of not wanting to do anything.

julia van schalkwyk

HaLlo Cort, it has been a long time since I left a reply. I am a accute EBV patient, and recemtly been diagnosed with liver hemangiomas, and mr scans showed no change there. I would like to know what role high uric acid has to play in accute ebv. Would it help if I try and follow a good anti-gout diet in keeping my t and b cells in better readings, and helping to fight the ebv better. I mentioned at that time that I got rid of the cfs for the first time in years, as soon as I start using the beriglobin, but after 6 months I stopped that, due to the fact that my specialist said it made my immunity system “lazy”. Can you reflect. On the uric acid please?

Cort Johnson

shathi

I’ve heard about a new ultraviolet machine called the UVLRx that’s being used for Epstein Barr patients. It uses a fiber optic thread which is inserted directly into the vein and the treatment lasts for an hour, so all the blood is treated. Has anyone tried this?

katwilm

sobnom

I’ve heard about a new ultraviolet machine called the UVLRx that’s being used for Epstein Barr patients. It uses a fiber optic thread which is inserted directly into the vein and the treatment lasts for an hour, so all the blood is treated. Has anyone tried this?

Linda

there is no CFS / MS virus that they know of. in my opinion as a CFS sufferer of 22 years, i would try an antiviral for the EBV and get the LTT ELISPOT test for Borrelia (Lyme)…i am not a medical professional..just a patient.

Kathleen

A long time ago I had CFS/fibromyalgia, diagnosed at the Cheney Clinic in Charlotte NC, Dr Cheney retired and closed the clinic years ago. I had the fatigue and aching that felt like it went all the way to the bones. In year 2000, a tooth got infected and had to be pulled, it had a root canal and a crown. The short of the story is the crown, it was white nickel, which I didn’t realize at the time it was done. Nickel is a toxic metal and has no place in the body. The day the tooth was pulled, all the fatigue and pain drained out of me and I’ve been well ever since. Since then, I go to a holistic dentist, had a dental material compatibility test, and we are careful about what goes in the teeth. I was sick for 20 years, amitrypteline and darvocet is what I was given for the pain and sleeplessnes in the years I was so sick. It seems there’s more than one way to get this condition. I also got the old amalgam fillings replaced with a safer composite filling. Best wishes and prayers to all of you looking for your help or cure.

Cort Johnson

Kathleen

Thanks for the comment Cort, the reason I’m reading this site is because I have a half sister who also has this condition. She had a bad case of mono about 10 years ago, and hasn’t been well since. I’m hoping to pick up some new info here that might help her. She’s so afraid to take the pain meds because she doesn’t want to become addicted, but, every Friday she takes one so she can drive to Texarkana to shop for her elderly mother. She says she feels like a new person on Fridays because she is almost pain free. We both suffered with allergies and yeast infections too. When I visited the Cheney Clinic, one suggestion he gave me to try was Milk Thistle herb capsules. It was such a good suggestion that I continue to use it daily. It helped me so much with the food allergies, everytime I ate anything, I took 2 caps right before. Milk Thistle is used in some hospitals in other countries for allergic reactions. It didn’t help my sister tho. I don’t really need it anymore, but I like to take it with meals, along with some other supplements to keep being healthy. It’s so strange that since that tooth got pulled in 2000, I haven’t even had a cold, once in a while I get a sinus infection, and I deal with it without antibiotics. I wish they would hurry up and find a good treatment for this awful stuff.

Karen Shaw

I have a hard time understanding all of this, mostly because I am ill and can take it all in I think. I have had Fibro 6 years that I think was active Mono that started it, been sick the whole 6 ys and then got his again 3 months ago with exact symptoms, I believe was sick 3 times in past 6 years that were like another activation. Never diagnosed with EBV till 3 months ago and it was active, told to come back and retest and the IGM came down to negative. Dr said had acute mono but the other levels remain elevated, pretty high not just elevated is what she said. Even after the IGM going to negative I am ILL very sickly feeling. Bloodwork is now all back to normal as calcium, sodium and albumin was high during infection and now normal. Nobody believes or gives thought to the fact that I feel very sick and it feels as it attacks different parts of my body. I swore I had a UTI, my bladder and kidney ached SO bad and one day blood in urine, was told kidney and bladder were fine, no infection and no enlargement. Having digestive issues and drenched clothing upon waking and have no fever. I honestly believe this is because of and still is somehow the EBV titers or virus. There seems to be no one in this city that can help or reaffirm that it is still the EBV virus or tell me what I can do about this. I am not well enough to advocate for myself and they don’t care to listen. Does this sound normal?? Where to start ,

Lauren

I have been reading this book called the medical medium and it talks about the EBV virus and how all kinds of illnesses are caused by this virus. Read this like it is very interesting. Hope this somewhat helps.

Lauren

Kelly

Here is a question. Are any of you effected by electro magnetic fields? I’m 35 recently thyroid cancer survivor of 2 months and then found auto immune and ebv in my system. What are your sensitivities? I have so many I’m chronically I’ll all the time and can’t functiion. Very saddened by all of this.

Paul

i have these symptoms but have not not all the tests referred to here (various blogs). I can functon but tire easily, lymphs start to hurt and have to rest. 18 years of being restricted, oh it is all so depressing, it affects relationships and how you feel about yourself. I am sitting here and can sense y lymph nodes in my throat feeling bruised and the ache going down under my arms, I am tired and now I have to do some work and focus is not east at all. But i WOULD LIKE TO SHARE THAT; I take coconut oil when its like this and it will knock it down -has anyone got another remedy I am so fed up with this ME/EBV…..

Janet

I got mono as a teen but have had reactivations of EBV all my life. I also was susceptible to other viruses like cytomegalovirus and parvo B19, and I even got West Nile three times. My immunologist was baffled because my serum complement and immune globulins were fine. I finally got this test which solved the mystery:

My body can’t convert “naive” B cells to mature cells, so I am unable to clear EBV and many other viruses. We did some more checking and found that I have a genetic mutation related to Severe Combined Immune Deficiency. With some immune deficiencies getting immune globulin therapy will clear the viruses, but I have very high antibodies to EBV, the problem is the B cells can’t respond to the signal from the antibodies.

Ian Francis

My doctor said, I have no immune response to the EBV, and that this is very strange because 99% of people have been exposed to it. I am still not sure what he meant or what blood test he based this on? Any ideas? (I can’t ask him because he is no longer my PCP).

Ian Francis

Thank you linda, that helps allot. The way he phrased it, it was like “Either….or….”. So there’s something wrong with my immune system if I’m not producing antibodies, I think that was on one end of it. And he made it sound like it’s very rare, whatever my situation. I need to dig and find those medical records, it was some kind of cutting edge blood test that he had to send away to be analyzed, but I recall from a couple years ago I couldn’t find it in the records.

julia

ian a hematologist usually test your T and B cells and treatment strive to balance the cells. the t cells fight viruses mostly and some bacterial infections and the b cells fight bacterial infections. tthe tests are called darkfield tests when the hematologist test for epstein barr virus that is active in the blood. then the mainstream drs test for the immuno globulins like IG, IGG, IGM etc. to test viral implication, and not necess active EB. when you were in hospital for serious operation etc your T cells may be compromised (due to medication, anti biotics, pain killers, operation itself etc) and it does take a long time to get them better. it does take a long time to get the right dr for tdiagnosis and treatment, since main stream drs don’t like to admit that they can’t see the problem. Bottomline, gp’s don’t specialize in EB and as a rule rules it out when they are not able to diagnose. Then still they refer you to psychologists etc. A lot still has to be learned from our immunity system. A lot of symptoms over lap and seems to be hormonal also. Eb is stealth in character. It hides and comes out when you have stress, hormonal as well. And emotional stress ranks very high here.

julia

I am also a non-secretor O and that means I have a lot of draw backs on lectines in food where, since I don’t have the protective mucus etc to protect my whole system harmful lectines in natural food (veg, fruit and legumes). That will mean that my first line of protection begins in the gut and it is already compromised there. It has a very neg effect on your overall health system and means and immunity system per se. It helps a lot to follow a blood group diet. To get your b and t cells in balancehelps tremendously in figting the eb. There is a lot of development in research on t and b cells and there is even evidence that when the t cells can’t do there work properly, they send signals to the b cells and that CFS and high B cells usually co-side. The best is to know your body and follow a correct diet for YOU! I don’t believe in mainstream med, because I am a non-secr and immuno compromised by default due to that! I will only follow mainstr if I have to… I always read the patients feed back when I have time because you learn a lot there. I have EB now for 7 years! Still not cleared. I took a beriglobin injection for less than a year and CFS went away for 3 years, now after a couple of majors operations it came back. Follow treatment to build immunity and have your b and t cells tested regularly and you will see the EB start to clear from the blood. Sorry about the spelling mistakes, touch screen!

Shelly

Thank you for this article, I have been scouring the web for days…I was diagnosed on Monday with CAEBV after following protocols to find the root cause of the Hashimotos’s Thyroiditis auto immune disorder…Everyone in my immediate family has an autoimune disorder…I was diagnosed with in two decades ago. Still trying to understand this CAEBV as my antibodies are off the charts along with the Hashi’s..double wammy…my whole body hurts and I keep getting the run around from infectious disease doctors..my primary is doing the best but he can not even read the labs. Called about a clinical trial in Bathesda Maryland…waiting on blood test DBA PCR test on whole blood. Is the the test that confirms or not? I live in Charlotte NC, and looking at some of the clinics mentioned I feel like I need to go the main stream docs right now, mostly for insurance and money is running low since I cant work..I am so sick, should I see an endocrinologist, immunologist, I am so confused.

Sue

I don’t doubt you have active EBV but from what I have read, true cases of CAEBV where the body is just not able to put it into latency, end up with cancers, etc. What you have sounds like good old fashioned CFS/ME to me. Have you tried Valtrex?
You may also want to get a Lyme test just in case (the LTT ELISPOT test).
I would see a CFS/ME specialist..I am not sure you will get anywhere with anyone else.